The number of HRP positive organelles in undamaged motoneurons and neurosecretory neurons after retrograde transport of the protein is about twice that following orthograde loading. The orthograde axoplasmic flow of HRP is very slight in these two classes of neurons in hydrated mice. After 5 days of drinking 2% NaC1 solutions, the anterograde flow is appreciably increased to neurosecretory neurons but not in motoneurons. That the HRP laden vacuoles in neurons are lysosomes is shown by simultaneous demonstration of HRP and acid phosphatose (ACP) activities in the same vacuole. In the GERL (Golgi associated smooth endoplasmic reticulum and lysosomes) cisterns of the somata of neurosecretory cells, the ACP activity diminishes while there is a concomitant rise in thiamine pyrophosphatose activity in the adjacent Golgi complex. Thus, prolonged osmotic stimulation results in an increase in metabolic and degradative enzymatic activities at the same time that the orthograde transfer of protein increases. The fall in ACP activity in the Gerl might reflect a diversion of degradative enzymatic activity to the lysosomes which are faced with an increased burden of protein.